We are investigating the origin and the significance of the tissue-specific variation in histone variant patterns in the mouse and the chicken in an attempt to elucidate the possible role of tightly bound chromosomal proteins in the stable alteration of the program of gene expression during normal cell differentiation and abnormalities thereof, such as cancer. Specifically we are studying a) the developmental program of expression of different histone variants in homogeneous populations of cell nuclei, b) the distribution of chromosomal proteins in different fractions of chromatin and c) the primary structure and the interactions of newly discovered histone variants and minor histone species.